Piwi–piRNA complexes induce stepwise changes in nuclear architecture at target loci

Yuka W. Iwasaki, Sira Sriswasdi, Yasuha Kinugasa, Jun Adachi, Yasunori Horikoshi, Aoi Shibuya, Wataru Iwasaki, Satoshi Tashiro, Takeshi Tomonaga, Haruhiko Siomi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs that form effector complexes with PIWI proteins (Piwi–piRNA complexes) and play critical roles for preserving genomic integrity by repressing transposable elements (TEs). Drosophila Piwi transcriptionally silences specific targets through heterochromatin formation and increases histone H3K9 methylation (H3K9me3) and histone H1 deposition at these loci, with nuclear RNA export factor variant Nxf2 serving as a co-factor. Using ChEP and DamID-seq, we now uncover a Piwi/Nxf2-dependent target association with nuclear lamins. Hi-C analysis of Piwi or Nxf2-depleted cells reveals decreased intra-TAD and increased inter-TAD interactions in regions harboring Piwi–piRNA target TEs. Using a forced tethering system, we analyze the functional effects of Piwi–piRNA/Nxf2-mediated recruitment of piRNA target regions to the nuclear periphery. Removal of active histone marks is followed by transcriptional silencing, chromatin conformational changes, and H3K9me3 and H1 association. Our data show that the Piwi–piRNA pathway can induce stepwise changes in nuclear architecture and chromatin state at target loci for transcriptional silencing.

Original languageEnglish
Article numbere108345
JournalEMBO Journal
Volume40
Issue number18
DOIs
Publication statusPublished - 2021 Sep 15

Keywords

  • RNA silencing
  • chromatin conformation
  • heterochromatin formation
  • nuclear localization
  • transcriptional regulation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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